Copper-catalyzed arylation of beta-amino alcohols

[reaction: see text] Methods for synthesizing N-aryl beta-amino alcohols and O-aryl beta-amino alcohols are described. The presence of a neighboring hydroxyl or amino group, respectively, is thought to activate beta-amino alcohols toward these transformations. These protocols significantly increase access to a variety of arylated beta-amino alcohols.     

Copper-catalyzed alkene arylation with diaryliodonium salts

Alkenes and arenes represent two classes of feedstock compounds whose union has fundamental importance to synthetic organic chemistry. We report a new approach to alkene arylation using diaryliodonium salts and Cu catalysis. Using a range of simple alkenes, we have shown that the product outcomes differ significantly from those commonly obtained by the Heck reaction. We have used these insights to develop a number of new tandem and cascade reactions that transform readily available alkenes into complex arylated products that may have broad applications in chemical synthesis.     

Copper-catalyzed arylation of indolin-2,3-ones with arylboronic acids

A convenient and efficient Cu(OTf)₂-catalyzed arylation of indolin-2,3-ones with arylboronic acids using cheap 1,10-phenanthroline hydrate as ligand was developed under air atmosphere, achieving 3-aryl-3-hydroxy-2-oxindoles in good to excellent yields. This catalytic system shows broad functional group tolerance. Moreover, the rigorous exclusion of air/moisture is not required in these transformations.     

Copper-catalyzed arylation of o-bromoanilides: highly flexible synthesis of hexahydropyrroloindole alkaloids

In the presence of catalytic amount of copper iodide, a remote amide-assisted intramolecular arylation followed by alkylation leads to a general and flexible synthetic method toward the synthesis of medicinally interesting hexahydropyrroloindole alkaloids.     

Copper-catalyzed oxidative sp3 C-H bond arylation with aryl boronic acids

An efficient method was developed for arylation of sp(3) C-H bonds using copper bromide as catalyst in absence of directing group with arylboronic acids. The oxidative arylation provides easy access to biologically active tetrahydroisoquinoline derivatives and can either use peroxide or molecular oxygen as oxidant.     

Copper-catalyzed arylation of amines using diphenyl pyrrolidine-2-phosphonate as the new ligand

[Chemical reaction: See text] We have developed a general, efficient, and inexpensive catalyst system for arylation of amines by using 10 mol % of CuI as the copper source, 20 mol % of diphenyl pyrrolidine-2-phosphonate (DPP) as the ligand, K3PO4 as the base, and DMF containing 2% water (v/v) as the solvent.     

Copper-catalyzed arylation of tetrazole-5-thiones upon convection heating and microwave activation conditions

The arylation of 1-phenyltetrazole-5-thione using a series of iodobenzene derivatives in the presence of cuprous chloride and a ligand such as ethylenediamine. It was shown that the use of microwave activation permitted shortening of the reaction time, increasing yields and simplification of the reaction products isolation.     

Copper-catalyzed "click" reaction/direct arylation sequence: modular syntheses of 1,2,3-triazoles

Inexpensive copper catalysts enabled modular one-pot multicomponent syntheses of fully decorated triazoles through a sustainable "click" reaction/direct arylation sequence.     

Copper-catalyzed arylation of phenylurea using KF/Al2O3

A mild and efficient method for the copper-catalyzed arylation of phenylurea is described. The coupling reaction of phenylurea with different functionalized aryl iodides in the presence of air stable CuI, N,N′-dibenzylethylenediamine as a ligand, and KF/Al₂O₃ as a base gives symmetrical and unsymmetrical diarylureas in relatively high yields.     

Copper-catalyzed cycloisomerizations of 5-en-1-yn-3-ols

[reaction: see text] The Cu(I)-catalyzed cycloisomerization of tertiary 5-en-1-yn-3-ols with an 1,2-alkyl shift affords stereoselectively tri- and tetracyclic compounds of high molecular complexity. These results are in agreement with a mechanism in which the cyclopropanation precedes the rearrangement.     

铜催化苯硼酸与苯并呋咱-1-氧化物的胺化反应

C-N键普遍存在于药物和有机功能分子中,传统构建C-N键的方法包括Goldberg反应、Buchwald-Hartwig偶联、Chan-Lam偶联和C-H键活化胺化.虽然这些方法都可以高效构建C-N键,但它们需要使用官能化的芳基底物、官能化的胺化试剂或在氧化条件下进行.理想的胺化反应应在氧化还原中性条件下进行,更为理想的则是在引入氨基的同时引入另外一个官能团.实现这个目标最直接的策略就是使用氮杂环,通过N-E(E=N或O)键的断裂,N原子和E原子可同时被引入.最近我们课题组利用氨茴内酐和氮杂苯并降冰片烯的C-H键活化反应成功实现了这种双官能团化.尽管该法很有吸引力,但是要通过氮杂环的断裂实现双官能团化,需要发生非张力环的开环,这在热力学上是非常不利的.苯并呋咱-1-氧化物可以开环得到邻二硝基苯中间体.基于对胺化反应的兴趣,我们推测苯并呋咱1-氧化物可以作为一个胺化试剂实现苯硼酸的胺化.尽管亚硝基苯对芳基硼酸进行简单的胺化已经被报道,但需要化学计量的铜盐,或是引入还原剂.因此本文报道铜催化的苯硼酸的胺化反应,该反应以苯并呋咱1-氧化物为胺化试剂,在温和及氧化还原中性条件下成功实现了双官能团化.本文共完成了31个不同官能团取代的硝基苯胺骨架结构的合成,反应均以中等到良好的收率得到目标产物,最高收率可达99%.为了增加反应的实用性,我们还进行了放大实验,实验表明,当苯并呋咱-1-氧化物的量由0.2 mmol放大至4 mmol时,反应仍能以较高的收率得到目标产物.此外,目标产物通过进一步的衍生化反应还可方便地转化为其他杂环类化合物.例如,在PPh3作用下,通过还原环化作用可生成吩嗪.在钯催化下可发生分子内碳氢键氧化反应得到咔唑类化合物.通过还原及重氮化反应还可方便地转化为苯并三唑.总之,我们以苯并呋咱-1-氧化物为胺化试剂,在铜催化下成功实现了苯硼酸的胺化反应,合成了一系列双官能团化产物.该催化体系反应条件温和,底物适用范围广,对各种官能团具有很好的兼容性.     

Copper-catalyzed tyrosine nitration

Tyrosine nitration, often observed during neurodegenerative disorders under nitrative stress, is usually considered to be induced chemically either by nitric oxide and oxygen forming nitrogen dioxide or by the decomposition of peroxynitrite. It can also be induced enzymatically by peroxidases or superoxide dismutases in the presence of both hydrogen peroxide and nitrite forming nitrogen dioxide and/or peroxynitrite. In this study, the role of cupric ions for catalyzing tyrosine nitration in the presence of hydrogen peroxide and nitrite, by a chemical mechanism rather similar to enzymatic pathways where nitrite is oxidized to form nitrogen dioxide, was investigated by development of a microreactor also capable of acting as an emitter for electrospray ionization mass spectrometry analysis. Indeed, cupric ions and peptide-cupric ion complexes are found to be excellent Fenton catalysts, even better than Fe(III) or heme, for the formation of (?)OH radicals and/or copper(II)-bound (?)OH radicals from hydrogen peroxide. These radicals are efficiently scavenged by nitrite anions to form (?)NO(2) and by tyrosine to form tyrosine radicals, leading to tyrosine nitration in polypeptides. We also show that cupric ions can catalyze tyrosine nitration from nitric oxide, oxygen, and hydrogen peroxide as the formation of tyrosine radicals is increased in the presence of diffusible and/or copper(II) bound hydroxyl radicals. This study shows that copper has a polyvalent role in the processes of tyrosine nitration.     

Copper-catalyzed multicomponent cascade process for the synthesis of hexahydro-1H-isoindolones

Copper-catalyzed coupling of imines, dienylstannanes, and acryloyl chlorides followed by a Diels-Alder reaction afforded hexahydro-1H-isoindolones. Diversification of the core via Pd-catalyzed cross-coupling defines a new modular approach to isoindolone combinatorial libraries.     

Copper-catalyzed N-arylation of oxindoles

The coupling of aryl bromides or iodides with oxindoles using a copper iodide-N,N′-dimethylethylene diamine system is presented. The reaction proceeds efficiently and tolerates a variety of substitution patterns.     

Copper-catalyzed functionalization of enynes

The copper-catalyzed functionalization of enyne derivatives has recently emerged as a powerful approach in contemporary synthesis. Enynes are versatile and readily accessible substrates that can undergo a variety of reactions to yield densely functionalized, enantioenriched products. In this perspective, we review copper-catalyzed transformations of enynes, such as boro- and hydrofunctionalizations, copper-mediated radical difunctionalizations, and cyclizations. Particular attention is given to the regiodivergent functionalization of 1,3-enynes, and the current mechanistic understanding of such processes.

The copper-catalyzed functionalization of enynes is a powerful approach to yield densely functionalized products. This review covers various transformations, such as boro- and hydrofunctionalizations, copper-mediated radical difunctionalizations, and cyclizations.